The specific aim will be to determine whether alterations in CNS GABAergic function will change coronary vascular resistance. Reasons for pursuing this aim are the findings that picrotoxin, a drug that blocks the effects of GABA, will cause sympathetically-mediated coronary vasoconstriction in cats, and increased sympathetic nervous system activity in patients may be an important factor causing Prinzmetal's Variant Angina. Cats will be anesthetized and an electromagnetic flow probe will be placed around the anterior descending branch of the left coronary artery. Using measurements of coronary flow during diastole and diastolic central aortic pressure, coronary vascular resistance will be determined before and after administering drugs which block CNS GABAergic mechanisms. Drugs which stimulate CNS GABAergic mechanisms will also be tested to determine whether these agents: (1) decrease coronary vascular resistance, and (2) prevent coronary constriction evoked by drugs which counteract the effects of GABA in the brain. The specific sympathetic fibers innervating the coronary vasculature and mediating coronary artery constriction will be determined by surgically transecting nerve branches prior to administering picrotoxin and noting whether or not decreases in the coronary vascular resistance occur. Finally, the location of GABA synapses in the CNS involved in evoking changes in coronary vascular resistance will be determined by microinjecting drugs which block CNS GABAergic mechanisms into specific brain regions known to utilize GABA as a transmitter and to exert control over sympathetic outflow to the heart. Data obtained from these studies should: (1) establish that changes in coronary blood flow can occur by altering the activity of a specific neurotransmitter in the brain, namely GABA, (2) define the sympathetic neural pathways innervating the coronary vasculature, causing vasospasm, and (3) provide the basis for developing new drugs (GABA mimetic agents) that could be used prophylactically to treat Prinzmetal's Angina.